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. 1970 Feb;49(2):373–380. doi: 10.1172/JCI106246

The integrity of the ether linkage during thyroxine metabolism in man

Constance S Pittman 1, Virginia H Read 1, Joseph B Chambers Jr 1, Haruyoshi Nakafuji 1
PMCID: PMC322479  PMID: 5411788

Abstract

The structures of thyroxine metabolites after total deiodination bear on the mode of thyroxine (T4) action in vivo. The present study was undertaken to determine the integrity of the ether linkage during thyroxine metabolism in man. Normal volunteers were given simultaneous intravenous injections of two thyroxines labeled with either 14C or 3H on the opposite sides of the ether linkage, D,L-[α,β-3H]T4 and D,L-[phenolic ring-14C]T4. The ratio of alanine side chain to phenolic ring which was measured as 3H:14C ratio was found to remain constant in the serum, urine, and feces during the subsequent 3 wk. The disappearance rates of the 3H and 14C radioactivity from blood were similar. The values of half-life were in the ranges of 4.2-6.7 days. 51-63% of the 3H and 50-57% of the 14C doses were recovered from urine and 13-20% of the 3H and 15-20% of the 14C doses were recovered from feces. Chromatography of the urinary metabolites confirmed that the phenolic ring and the nonphenolic ring including at least part of the side chain remained linked together.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALBERT A., RALL J. E. The behavior of labeled thyroglobulin and labeled thyroxine in patients with myxedema. J Clin Endocrinol Metab. 1949 Dec;9(12):1392–1405. doi: 10.1210/jcem-9-12-1392. [DOI] [PubMed] [Google Scholar]
  2. DUNN J. T., WERNER S. C. METABOLISM OF L-THYROXINE (3:5-131-I) IN MAN. J Clin Endocrinol Metab. 1964 May;24:460–466. doi: 10.1210/jcem-24-5-460. [DOI] [PubMed] [Google Scholar]
  3. Harington C. R., Salter W. T. The isolation of l-thyroxine from the thyroid gland by the action of proteolytic enzymes. Biochem J. 1930;24(2):456–471. doi: 10.1042/bj0240456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. INGBAR S. H., FREINKEL N. Simultaneous estimation of rates of thyroxine degradation and thyroid hormone synthesis. J Clin Invest. 1955 Jun;34(6):808–819. doi: 10.1172/JCI103136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. LISSITZKY S., BENEVENT M. T., ROQUES M., ROCHE J. Caractérisation de la thyronine comme produit de la désiodation de la thyroxine par des coupes de foie de rat. C R Seances Soc Biol Fil. 1958;152(11):1490–1491. [PubMed] [Google Scholar]
  6. PLASKETT L. G. Studies on the degradation of thyroid hormones in vitro with compounds labelled in either ring. Biochem J. 1961 Mar;78:652–657. doi: 10.1042/bj0780652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Pittman C. S., Chambers J. B., Jr The carbon structure of thyroxine metabolites in urine. Endocrinology. 1969 Apr;84(4):705–710. doi: 10.1210/endo-84-4-705. [DOI] [PubMed] [Google Scholar]
  8. Pittman C. S., Maruyama T., Chambers J. B., Jr Metabolism of the diiodotyrosyl moiety of specifically labeled thyroxines. Endocrinology. 1968 Sep;83(3):489–494. doi: 10.1210/endo-83-3-489. [DOI] [PubMed] [Google Scholar]
  9. Pittman C. S., Shimizu C. Metabolism of 131-I- and 14-C-labeled thyroxines. Endocrinology. 1966 Dec;79(6):1109–1116. doi: 10.1210/endo-79-6-1109. [DOI] [PubMed] [Google Scholar]
  10. ROCHE J., NUNEZ J., JACQUEMIN C. [Nature of the deiodination products of thyroid hormones labelled simultaneously with tritium and radioactive iodiine]. Biochim Biophys Acta. 1962 Nov 5;64:475–486. doi: 10.1016/0006-3002(62)90305-0. [DOI] [PubMed] [Google Scholar]
  11. STERLING K., LASHOF J. C., MAN E. B. Disappearance from serum of I131-labeled l-thyroxine and l-triiodothyronine in euthyroid subjects. J Clin Invest. 1954 Jul;33(7):1031–1035. doi: 10.1172/JCI102970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. TAPLEY D. F., DAVIDOFF F. F., HATFIELD W. B., ROSS J. E. Physiological disposition of D- and L-thyroxine in the rat. Am J Physiol. 1959 Nov;197:1021–1027. doi: 10.1152/ajplegacy.1959.197.5.1021. [DOI] [PubMed] [Google Scholar]
  13. WEST C. D., SIMONS E. L., GORTATOWSKI M. J., KUMAGAI L. F. The metabolism of ring-labeled L-thyroxine-C14 in vivo. J Clin Invest. 1963 Jul;42:1134–1141. doi: 10.1172/JCI104798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. WYNN J., GIBBS R. Thyroxine degradation. II. Products of thyroxine degradation by rat liver microsomes. J Biol Chem. 1962 Nov;237:3499–3505. [PubMed] [Google Scholar]

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